Dr. Dallabrida is an instructor with training in molecular biology and angiogenesis. Her long-term career goal is to become an independent investigator in vascular biology and to focus on translational research. Toward this goal, she committed three years of post-doctoral work and one year as an instructor to determine the role of vascular maturation in regulating adipose tissue growth and regression. These studies were done in her sponsor's laboratory (Dr. Rupnick) as part of an effort to assess the role of endothelial cell regulation of normal tissue growth. In the Surgical Research Division, Dr. Dallabrida contributes to an established program dedicated to angiogenesis-based studies under the direction of her co-sponsor, Dr. Folkman, who is the recognized founder of the angiogenesis field. A KO1 award would facilitate her transition from an instructor to an independent investigator by enabling additional training and research experiences via collaborations, participation in annual national/international meetings, and a biostatistics course. Her career development plan includes diversification of research skills, a workshop on grant writing, training in the responsible conduct of science, human subjects research training, laboratory meetings, and seminars. The research project will test the hypothesis that adipose tissue vasculature is chronically immature, thereby preserving its plasticity and capacity for remodeling after development. Dr. Rupnick's and Dr. Dallabrida's earlier work showed that the supporting vasculature is uniquely plastic and susceptible to angiogenesis inhibitors. Mature vascular beds do not typically have these characteristics. Immature vessels, however, would be readily able to grow or regress, and respond to antiangiogenic agents. Dr. Dallabrida's immediate goals are to further these investigations and expand them to include human tissue. The hypothesis will be tested through the following specific aims: 1) Characterize the expression and functional role of angiopoietins and tie receptors, regulators of vessel maturation, in adipose tissue during growth or regression using mouse models of obesity. 2) Characterize the role of vascular maturation in aberrant adipose tissue, such as lipomatosis. Dr. Dallabrida will examine the angiopoietin/tie2 system in human samples and determine the relevance of perturbations in this system to disease persistence. A KO1 award would advance these research efforts and her transition to independence as an investigator.